Studies on the transformation of engineered nanomaterials (ENMs) based on relevant environmental exposure scenarios are scarce. In this context, we investigated the use of Transmission Electron Microscopy (TEM) grids to expose minute amounts of ZnO and Ag nanoparticles (NPs) to artificial and natural aqueous media and follow their transformation using scanning transmission electron microscopy coupled with energy dispersive X-ray spectroscopy. Short-term experiments conducted with inorganic sulfides confirmed the potential of using TEM grids to monitor the transformation of ENMs at the single particle level. After 30 min, Ag NPs transformed into Ag-sulfides, with Ag : S ratios ≈ 2 : 1, while ZnO NPs showed little evidence of Zn-sulfides precipitation after 6 hours. Ag NPs and ZnO NPs were also exposed to depth-dependent pore water concentration gradients in freshwater sediment columns. After three days and four weeks, all the Ag NPs observed were transformed into Ag-sulfides with various morphologies and Ag : S ratios (1 ≤ Ag/S ≤ 2), depending on the depth and duration of the exposure. Furthermore, a depth-dependent transformation was observed for ZnO NPs. At low sulfide concentration, in the first millimeters below the water-sediment interface, ZnO NPs were completely transformed into ZnS harboring empty shell structures, together with smaller particles in their vicinity. By contrast, ZnO cores persisted in the deeper layers, indicating that ZnO NPs dissolution was inhibited at high sulfide concentrations. Our results demonstrate the advantage of experimental and analytical strategies adapted to study the transformation of ENMs under environmentally relevant conditions, to unravel transformation rates and products not yet considered in risk assessment studies.